The Canadian Open Neuroscience Platform-An open science framework for the neuroscience community.

The Canadian Open Neuroscience Platform (CONP) takes a multifaceted approach to enabling open neuroscience, aiming to make research, data, and tools accessible to everyone, with the ultimate objective of accelerating discovery. Its core infrastructure is the CONP Portal, a repository with a decentralized design, where datasets and analysis tools across disparate platforms can be browsed, searched, accessed, and shared in accordance with FAIR principles. Another key piece of CONP infrastructure is NeuroLibre, a preprint server capable of creating and hosting executable and fully reproducible scientific publications that embed text, figures, and code.

BigNeuron: a resource to benchmark and predict performance of algorithms for automated tracing of neurons in light microscopy datasets.

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms.

HDAC inhibition leads to age-dependent opposite regenerative effect upon PTEN deletion in rubrospinal axons after SCI.

Epigenetic changes associated with aging have been linked to functional and cognitive deficits in the adult CNS. Histone acetylation is involved in the control of the transcription of plasticity and regeneration-associated genes. The intrinsic axon growth capacity in the CNS is negatively regulated by phosphatase and tensin homolog (Pten).

Power to the People: Addressing Big Data Challenges in Neuroscience by Creating a New Cadre of Citizen Neuroscientists.

Global neuroscience projects are producing big data at an unprecedented rate that informatic and artificial intelligence (AI) analytics simply cannot handle. Online games, like Foldit, Eterna, and Eyewire-and now a new neuroscience game, Mozak-are fueling a people-powered research science (PPRS) revolution, creating a global community of "new experts" that over time synergize with computational efforts to accelerate scientific progress, empowering us to use our collective cerebral talents to drive our understanding of our brain.

SPARC expression by cerebral microvascular endothelial cells in vitro and its influence on blood-brain barrier properties.

Background: SPARC (secreted protein acidic and rich in cysteine) is a nonstructural, cell-matrix modulating protein involved in angiogenesis and endothelial barrier function, yet its potential role in cerebrovascular development, inflammation, and repair in the central nervous system (CNS) remains undetermined.

Methods: This study examines SPARC expression in cultured human cerebral microvascular endothelial cells (hCMEC/D3)-an in vitro model of the blood-brain barrier (BBB)-as they transition between proliferative and barrier phenotypes and encounter pro-inflammatory stimuli. SPARC protein levels were quantified by Western blotting and immunocytochemistry and messenger RNA (mRNA) by RT-PCR.

BigNeuron: Large-Scale 3D Neuron Reconstruction from Optical Microscopy Images.

Understanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and standardization to provide a community resource for automated reconstruction of dendritic and axonal morphology of single neurons.

Epigenetics of neural repair following spinal cord injury.

Spinal cord injury results from an insult inflicted on the spinal cord that usually encompasses its 4 major functions (motor, sensory, autonomic, and reflex). The type of deficits resulting from spinal cord injury arise from primary insult, but their long-term severity is due to a multitude of pathophysiological processes during the secondary phase of injury. The failure of the mammalian spinal cord to regenerate and repair is often attributed to the very feature that makes the central nervous system special-it becomes so highly specialized to perform higher functions that it cannot effectively reactivate developmental programs to re-build novel circuitry to restore function after injury.

Olfactory ensheathing cells promote corticospinal axonal outgrowth by a L1 CAM-dependent mechanism.

Olfactory ensheathing cells (OECs) support the ability of the olfactory neuraxis to continually retarget within the mature central nervous system. This has led many groups to transplant OECS into the lesioned rodent spinal cord (SCd) in vivo, with variable degrees of anatomical, physiological, and behavioral success. Some of the most conflicting results in OEC transplantation have come from the corticospinal tract (CST) which has shown a relatively poor regeneration response.

HDAC inhibitors dysregulate neural stem cell activity in the postnatal mouse brain.

The mammalian central nervous system (CNS) undergoes significant expansion postnatally, producing astrocytes, oligodendrocytes and inhibitory neurons to modulate the activity of neural circuits. This is coincident in humans with the emergence of pediatric epilepsy, a condition commonly treated with valproate/valproic acid (VPA), a potent inhibitor of histone deacetylases (HDACs). The sequential activity of specific HDACs, however, may be essential for the differentiation of distinct subpopulations of neurons and glia.

SPARC regulates microgliosis and functional recovery following cortical ischemia.

Secreted protein acidic rich in cysteine (SPARC) is a matricellular protein that modulates the activity of growth factors, cytokines, and extracellular matrix to play multiple roles in tissue development and repair, such as cellular adhesion, migration, and proliferation. Throughout the CNS, SPARC is highly localized in mature ramified microglia, but its role in microglia--in development or during response to disease or injury--is not understood. In the postnatal brain, immature amoeboid myeloid precursors only induce SPARC expression after they cease proliferation and migration, and transform into mature, ramified resting microglia.

Fibroblast growth factor signaling regulates neurogenesis at multiple stages in the embryonic olfactory epithelium.

Lifelong neurogenesis in the mouse olfactory epithelium (OE) is regulated by the response of stem/progenitor cells to local signals, but embryonic and adult OE progenitors appear to be quite different--with potentially different mechanisms of regulation. A recently identified progenitor unique to embryonic OE--the nestin+ radial glial-like progenitor--precedes some Mash1+ progenitors in the olfactory receptor neuron (ORN) lineage, which then gives rise to immediate neuronal precursors and immature ORNs. Neurogenic drive at each stage is governed largely by exogenous factors.

SPARC-like 1 (SC1) is a diversely expressed and developmentally regulated matricellular protein that does not compensate for the absence of SPARC in the CNS.

SPARC-like 1 (SC1) is a member of the SPARC family of matricellular proteins that has been implicated in the regulation of processes such as cell migration, proliferation, and differentiation. Here we show that SC1 exhibits remarkably diverse and dynamic expression in the developing and adult nervous system. During development, SC1 localizes to radial glia and pial-derived structures, including the vasculature, choroid plexus, and pial membranes.

Epigenetics DNA methylation in the core ataxin-2 gene promoter: novel physiological and pathological implications.

Pathogenic CAG (cytosine-adenine-guanine) expansions beyond certain thresholds in the ataxin-2 (ATXN2) gene cause spinocerebellar ataxia type 2 (SCA2) and were shown to contribute to Parkinson disease, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Regulation of ATXN2 gene expression and the function of the protein product are not known. SCA2 exhibits an inverse correlation between the size of the CAG repeat and the age at disease onset.

Adult spinal cord radial glia display a unique progenitor phenotype.

Radial glia (RG) are primarily embryonic neuroglial progenitors that express Brain Lipid Binding Protein (Blbp a.k.a.

Combination of olfactory ensheathing cells with local versus systemic cAMP treatment after a cervical rubrospinal tract injury.

The failure of CNS axons to regenerate following traumatic injury is due in part to a growth-inhibitory environment in CNS as well as a weak intrinsic neuronal growth response. Olfactory ensheathing cell (OECs) transplants have been reported to create a favorable environment promoting axonal regeneration, remyelination, and functional recovery after spinal cord injury. However, in our previous experiments, OEC transplants failed to promote regeneration of rubrospinal axons through and beyond the site of a dorsolateral funiculus crush in rats.

MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons.

DNA methylation-dependent gene silencing is initiated by DNA methyltransferases (DNMTs) and mediated by methyl-binding domain proteins (MBDs), which recruit histone deacetylases (HDACs) to silence DNA, a process that is essential for normal development. Here, we show that the MBD proteins MBD2 and MeCP2 regulate distinct transitional stages of olfactory receptor neuron (ORN) differentiation in vivo. Mbd2 null progenitors display enhanced proliferation, recapitulated by HDAC inhibition, and Mbd2 null ORNs have a decreased lifespan.

Epigenetic regulation of nervous system development by DNA methylation and histone deacetylation.

Alterations in the epigenetic modulation of gene expression have been implicated in several developmental disorders, cancer, and recently, in a variety of mental retardation and complex psychiatric disorders. A great deal of effort is now being focused on why the nervous system may be susceptible to shifts in activity of epigenetic modifiers. The answer may simply be that the mammalian nervous system must first produce the most complex degree of developmental patterning in biology and hardwire cells functionally in place postnatally, while still allowing for significant plasticity in order for the brain to respond to a rapidly changing environment.

Corticospinal neurons respond differentially to neurotrophins and myelin-associated glycoprotein in vitro.

Elucidating the mechanisms that regulate the survival and outgrowth of corticospinal tract (CST) neurons and other CNS tracts will be a key component in developing novel approaches for the treatment of central nervous system (CNS) disorders, including stroke, spinal cord injury (SCI), and motor neuron disease (MND). However, the in vivo complexities of these diseases make a systematic evaluation of potential therapeutics that directly affect corticospinal regeneration or survival very challenging. Here, we use Thy1.

Undesired effects of a combinatorial treatment for spinal cord injury--transplantation of olfactory ensheathing cells and BDNF infusion to the red nucleus.

Transplantations of olfactory ensheathing cells (OECs) have been reported to promote axonal regeneration and functional recovery after spinal cord injury, but have demonstrated limited growth promotion of rat rubrospinal axons after a cervical dorsolateral funiculus crush. Rubrospinal neurons undergo massive atrophy after cervical axotomy and show only transient expression of regeneration-associated genes. Cell body treatment with brain-derived neurotrophic factor (BDNF) prevents this atrophy, stimulates regeneration-associated gene expression and promotes regeneration of rubrospinal axons into peripheral nerve transplants.

Histone deacetylases 1 and 2 are expressed at distinct stages of neuro-glial development.

The deacetylation of histone proteins, catalyzed by histone deacetylases (HDACs), is a common epigenetic modification of chromatin, associated with gene silencing. Although HDAC inhibitors are used clinically to treat nervous system disorders, such as epilepsy, very little is known about the expression pattern of the HDACs in the central nervous system. Identifying the cell types and developmental stages that express HDAC1 and HDAC2 within the brain is important for determining the therapeutic mode of action of HDAC inhibitors, and evaluating potential side effects.

A novel embryonic nestin-expressing radial glia-like progenitor gives rise to zonally restricted olfactory and vomeronasal neurons.

Persistent neurogenesis is maintained throughout development and adulthood in the mouse olfactory epithelium (OE). Despite this, the identity and origin of different embryonic OE progenitors, their spatiotemporal induction and contribution to patterning during development, has yet to be delineated. Here, we show that the embryonic OE contains a novel nestin-expressing radial glia-like progenitor (RGLP) that is not found in adult OE, which is antigenically distinct from embryonic CNS radial glia.

Culturing olfactory ensheathing cells from the mouse olfactory epithelium.

Olfactory ensheathing cells (OECs) are not a class of stem cell, but they are a specialized and highly plastic glial cell that can continuously support the neurogenesis and axonal regeneration of olfactory receptor neurons. Because of this, they have been transplanted into sites of spinal cord injury to test their efficacy in promoting repair. They also have been demonstrated to have some ability to support the remyelination of demyelinated axons.

Olfactory ensheathing cells: isolation and culture from the neonatal olfactory bulb.

Olfactory ensheathing cells (OECs), which are glia from the olfactory system, have evolved as attractive candidates for transplant-mediated repair based on long-standing knowledge that the olfactory system is one of the only central nervous system tissues that can support neurogenesis throughout life. After injury and during normal cell turnover, the olfactory receptor neurons (ORNs) die, and new nerves are generated from putative stem cells in the olfactory epithelium. OECs, which reside throughout the olfactory system, guide the ORN axons as they travel through the olfactory mucosa (olfactory epithelium and lamina propria) and the cribriform plate, terminating in synapse formation in the usually nonpermissive environment of the olfactory bulb.